Methods for the amplification of nucleic acids are known in the art. The patent specification U.S. Pat. No. 4,683,202 discloses a process for amplifying a specific nucleic acid sequence contained in a nucleic acid or a mixture of nucleic acids, wherein each nucleic acid consists of two separate complementary strands, of equal or unequal length. The process comprises: (a) treating the strands with two oligonucleotide primers, for each different specific sequence being amplified, under conditions such that for each different sequence being amplified an extension product of each primer is synthesised which is complementary to each nucleic acid strand, wherein said primers are selected so as to be sufficiently complementary to different strands of each specific sequence such that the extension product synthesised from one primer, when it is separated from its complement, can serve as a template for synthesis of the extension product of the other primer; (b) separating the primer extension products from the templates on which they were synthesised to produce single-stranded molecules; and (c) treating the single-stranded molecules generated from step (b) with the primers of step (a) under conditions that a primer extension product is synthesised using each of the single strands produced in step (b) as a template. The steps can be carried out consecutively or simultaneously. Furthermore, the steps (b) and (c) can be repeated until the desired extent of sequence amplification has been achieved. In the case that in the process the steps (a) and (c) are performed using a polymerase, the process is commonly referred to as polymerase chain reaction (PCR).
The international patent application WO 2007/143034 A1 discloses methods, which are supposedly suitable for the execution of PCR. The methods may comprise the use of an optical source to provide heating in a PCR. The methods may also include the use of surface plasmon resonance or fluorescence resonance energy transfer to allow real-time monitoring of a PCR reaction. The methods may comprise immobilising a template, primer or polymerase on a surface such as a gold or on another surface plasmon resonance active surface.
The patent application US 2002/0061588 A1 discloses methods for rendering nucleic acids locally and directly responsive to an external signal. The signal acts exclusively on one or several specific, localised parts of the nucleic acid. According to the invention, the signal can change the properties of a specific nucleic acid and thereby modify its function. Thus, the invention provides methods, which control the structure and function of a nucleic acid in a biological sample without influencing other parts of the sample. In one embodiment, a modulator transfers heat to a nucleic acid or a part of a nucleic acid, which results, e.g., in a destabilisation of inter- or intramolecular bonds and in an alteration of structure and stability of the nucleic acid. Preferred modulators include metal nanoparticles, semiconducting nanoparticles, magnetic nanoparticles, oxide nanoparticles and chromophores. It is also suggested, to use these methods in conjunction with PCR. Particularly, it is proposed to control a PCR reaction with a modulator.
The patent application US 2003/0143604 A1 concerns the use of nanoparticle detection probes to monitor amplification reactions, in particular PCR. Especially, the patent application deals with the use of nanoparticle oligonucleotide conjugates treated with a protective agent such as bovine serum albumin in order to quantitatively and qualitatively detect a target polynucleotide. The patent application discloses a nucleic acid amplification and detection using gold nanoparticle primers. In a first step, the nucleic acid target is denatured in the presence of the gold nanoparticles that are functionalised with primers. In a second step, the gold nanoparticles and the oligonucleotides attached thereto hybridise with the nucleic acid target and a copy of the complementary DNA sequence is produced starting from the nucleic acid primers, which are attached to the nanoparticles. The steps one and two are repeated and the optical signal, which is created by the binding of amplified complementary nanoparticle probes, is detected.